Work in progress has indicated that there is a lower mean value for sodium pump activity in erythrocytes from subjects who have a history of bipolar manic-depressive psychosis, as compared with controls; the difference appears to be specific for bipolar or unipolar-manic disorder. The proposed work includes studies of erythrocyte sodium pump values from bipolar subjects during episodes of mania and during episodes of depression, and individual fluctuations in erythrocyte sodium pump and membrane NaK-ATPase activities in a selected group of subjects and controls over the course of five years. The effect of lithium therapy on erythrocyte sodium pump and membrane NaK-ATPase activities and on the phospholipid composition of erythrocyte cell membranes will be determined. The characteristics of the erythrocyte NaK-ATPase will be studied in an attempt to determine whether a genetic variant is involved in bipolar manic-depressive psychosis. The possibility of developing a diagnostic test based on the observations will be explored. Phospholipid levels and phospholipid metabolism in erhthrocyte membranes from subjects with various functional psychoses will be measured. Particular objectives in this area are: To determine the relationship of phosphatidylserine levels to sodium pump activity in erythrocytes in bipolar manic-depressive psychosis, to determine relative levels of phosphatidylcholine and phosphatidylethanolamine in erythrocyte membranes in schizophrenia, and to study the metabolism of phosphatidic acid and polyphosphoinositides in erythrocyte membranes in the different functional psychoses. In pharmacological studies with animals, the effects of chronic administration of lithium salts on the levels of NaK-ATPase and on levels of individual phospholipids in rat and mouse brain will be assayed.